The innervation of the pulp-dentin complex is of major health importance because it mediates dental pain and serves poorly understood functions in maintaining the vitality of teeth and in inflammation and repair of dental tissues. Moreover, mammalian teeth are intriguing targets of sensory innervation because of their late (postnatal) development and because they have a rich nociceptive innervation confined within a rigid well-defined pulp chamber. In order to develop therapeutic strategies, it is essential that the biological properties of neurons that innervate the dental pulp be better defined. Thus, the long-term objective of this research program is to define the extent to which the dental pulp and its innervation interact during development and in response to injury, and ultimately to elucidate the mechanisms for this interaction. The underlying hypothesis is that specific neurotrophic factors act as mediators by which dental tissues selectively influence the different subpopulations of sensory neurons that innervate them. Work in this laboratory has demonstrated that one class of dental sensory neurons fails to develop in response to postnatal deprivation of one such factor, nerve growth factor. The goals of the proposed studies are to (1) determine how many distinct populations of sensory neurons supply the dental pulp and to define the phenotypic features of these populations, (2) develop and utilize an experimental system that permits assessment of responses to tooth injury by sensory neurons, and (3) characterize expression of neurotrophic signals by non-neural pulp cells. Trigeminal neurons that project to the molar pulp in the rat will be identified by application of a persistent retrograde tracer under conditions that minimize injury and allow for complete healing. This will permit precise characterization of dental neurons with respect to (a) morphology, (b) expression of cytochemical markers, and (c) the specific neurotrophic factor to which they are potentially responsive. In order to identify neuronal responses to tooth injury, the same parameters will be examined over time in neurons that have been labeled before the pulp-dentin complex is subjected to injuries.